title: Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a major inflammatory condition of the skin caused by inherited skin barrier deficiency, with mutations in the filaggrin gene predisposing to development of AD. Support for barrier deficiency initiating AD came from flaky tail mice, which have a frameshift mutation in Flg and also carry an unknown gene, matted, causing a matted hair phenotype.
  
  
  OBJECTIVE
  We sought to identify the matted mutant gene in mice and further define whether mutations in the human gene were associated with AD.
  
  
  METHODS
  A mouse genetics approach was used to separate the matted and Flg mutations to produce congenic single-mutant strains for genetic and immunologic analysis. Next-generation sequencing was used to identify the matted gene. Five independently recruited AD case collections were analyzed to define associations between single nucleotide polymorphisms (SNPs) in the human gene and AD.
  
  
  RESULTS
  The matted phenotype in flaky tail mice is due to a mutation in the Tmem79/Matt gene, with no expression of the encoded protein mattrin in the skin of mutant mice. Matt(ft) mice spontaneously have dermatitis and atopy caused by a defective skin barrier, with mutant mice having systemic sensitization after cutaneous challenge with house dust mite allergens. Meta-analysis of 4,245 AD cases and 10,558 population-matched control subjects showed that a missense SNP, rs6684514, [corrected] in the human MATT gene has a small but significant association with AD.
  
  
  CONCLUSIONS
  In mice mutations in Matt cause a defective skin barrier and spontaneous dermatitis and atopy. A common SNP in MATT has an association with AD in human subjects.
authors.affiliation: School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Saunders
authors.forename: Christabelle S M
authors.initials: CS
authors.lastname: Goh
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Brown
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Porter
authors.forename: Christian
authors.initials: C
authors.lastname: Cole
authors.forename: Linda E
authors.initials: LE
authors.lastname: Campbell
authors.forename: Marek
authors.initials: M
authors.lastname: Gierlinski
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Barton
authors.forename: Georg
authors.initials: G
authors.lastname: Schneider
authors.forename: Allan
authors.initials: A
authors.lastname: Balmain
authors.forename: Alan R
authors.initials: AR
authors.lastname: Prescott
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Baurecht
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Lee
authors.forename: Roger
authors.initials: R
authors.lastname: Tavendale
authors.forename: Somnath
authors.initials: S
authors.lastname: Mukhopadhyay
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Turner
authors.forename: Vishnu B
authors.initials: VB
authors.lastname: Madhok
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sullivan
authors.forename: Caroline
authors.initials: C
authors.lastname: Relton
authors.forename: John
authors.initials: J
authors.lastname: Burn
authors.forename: Simon
authors.initials: S
authors.lastname: Meggitt
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Smith
authors.forename: Michael A
authors.initials: MA
authors.lastname: Allen
authors.forename: Jonathan N W N
authors.initials: JN
authors.lastname: Barker
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Reynolds
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
authors.forename: Alan D
authors.initials: AD
authors.lastname: Irvine
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Aileen
authors.initials: A
authors.lastname: Sandilands
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
mesh_terms: D000818:Animals; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000091344:Filaggrin Proteins; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009154:Mutation; D010641:Phenotype; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D008565:Membrane Proteins; C585426:Tmem79 protein, human; C585425:Tmem79 protein, mouse
keywords: AD; Allergy; Atopic dermatitis; DM; Double mutant; FLG; Filaggrin; HDM; High-power field; House dust mite; MAPEG; Matt; Membrane-associated proteins in eicosanoid and glutathione metabolism; OR; Odds ratio; SNP; Single nucleotide polymorphism; TEWL; Tmem79; Transepidermal water loss; WT; Wild-type; association; atopic dermatitis; atopy; eczema; filaggrin; flaky tail; hpf; mattrin; mouse; mutation